Assessment of occupational exposure to cytotoxic drugs by urinary or surface sampling

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OLYMPUS DIGITAL CAMERAOccupational exposures to cytotoxic drugs, particularly in hospitals, must be assessed and controlled owing to the mutagenic, carcinogenic and teratogenic character of certain of these compounds. In this context, INRS has developed an exposure assessment strategy based on urinary biomonitoring and measurement of surface contamination. This concern is shared by IOCOEM (Institute and Outpatient Clinic for Occupational and Environmental Medicine) of the University of Munich (Germany), which has also developed an assessment strategy based exclusively on measuring of surface contamination and has published guidance values for 5-fluorouracile.

A partnership focusing on 5-fluorouracile was concluded with IOCOEM to compare these two assessment methods in two hospitals in Germany and two hospitals in France.

Moreover, the assessment was extended to other cytotoxic drugs (cyclophosphamide, ifosfamide, methotrexate) and to a higher number of employees in the two French hospitals retained within the framework.

APPROACH

An assessment of exposures to 5-fluorouracile by urinary biomonitoring and by measuring surface contamination was conducted in Germany and in France. Some ten people (pharmacy technicians, nurses, health carers) were followed up in each hospital (pharmacies and healthcare departments). The surface samples (laboratory bench tops, floors, etc.) were taken in the same departments. α-fluoro-β-alanine (FBAL), a urinary metabolite of 5-fluorouracile, was quantified in the urine samples by INRS, and OCOEM ensured the analysis of 5-fluorouracile in the surface samples.

In addition, the complete assessment of exposures in the two French hospitals concerned 44 and 50 people respectively. The quantitative analysis of the biomarkers of exposure to cyclophosphamide, ifosfamide, methotrexate and 5-fluorouracile was conducted in urines, and cyclophosphamide, ifosfamide and 5-fluorouracile were quantified in different surface samples.

MAIN RESULTS

The surface samples revealed generally higher contaminations in the pharmacies of the French hospitals. On the other hand, regarding the healthcare departments, the contaminations were systematically higher in Germany. The biomonitoring data show significant urinary excretions of FBAL, highlighting employee exposure to 5-fluorouracile in all the hospitals, with no relationship with the surface contaminations. However, no difference was observed between French and German hospitals.

Regarding the second part of the study, very significant urinary excretions and surface contaminations were highlighted in both French hospitals.

DISCUSSION

It would appear, in the light of these data, that employee contamination is not linked to that of work surfaces. This measurement alone is not enough to estimate staff exposure or to guarantee its control. Biomonitoring most definitely must be employed. It is this assessment strategy that was adopted by INRS.

The second part of this study confirmed the aforementioned conclusions. The exposures highlighted in both hospitals show that it is still necessary to improve the prevention measures applied, in every department and for every professional category. These prevention measures have been the subject of an information brochure « Cytotoxic drugs and healthcare workers. Handle with caution » published with the reference INRS ED 6138.

Contact: Sophie Ndaw – Toxicology and Biometrology Division: sophie.ndaw@inrs.fr

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